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Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation
Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. We have previously shown that arachidonate 15-lipoxygenase B (ALOX15B) is highly expressed in atherosclerotic carotid plaques, and elucidation of mechanisms downstream of activated lipoxygenases may...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922896/ https://www.ncbi.nlm.nih.gov/pubmed/24533104 http://dx.doi.org/10.1371/journal.pone.0088546 |
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author | Vijil, Carolina Hermansson, Cecilia Jeppsson, Anders Bergström, Göran Hultén, Lillemor Mattsson |
author_facet | Vijil, Carolina Hermansson, Cecilia Jeppsson, Anders Bergström, Göran Hultén, Lillemor Mattsson |
author_sort | Vijil, Carolina |
collection | PubMed |
description | Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. We have previously shown that arachidonate 15-lipoxygenase B (ALOX15B) is highly expressed in atherosclerotic carotid plaques, and elucidation of mechanisms downstream of activated lipoxygenases may be relevant to our understanding of the genesis of atherosclerotic diseases. We examined 120 carotid plaques from patients with symptomatic carotid artery stenosis and showed that the extent of ALOX15B staining was significantly increased in carotid plaques with thrombosis. Impedance aggregometry analyses showed that the ALOX15B enzyme products 15-HETE and 15-HPETE increased platelet aggregation. By using a calibrated automatic thrombin assay, we showed that the ALOX15B products also increased both peak levels of thrombin and the total endogenous thrombin potential. Moreover, platelet aggregation was increased by addition of cell lysates from ischemic human macrophages, whereas platelet aggregation was reduced after knockdown of ALOX15B in human macrophages. Our data show that ALOX15B expression in human carotid plaques is associated with thrombus formation and that enzyme products of ALOX15B increase platelet aggregation and thrombin generation. We therefore propose that activated ALOX15B in macrophages may play a role in the induction of atherothrombotic events by increasing platelet aggregation and thrombin generation. |
format | Online Article Text |
id | pubmed-3922896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39228962014-02-14 Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation Vijil, Carolina Hermansson, Cecilia Jeppsson, Anders Bergström, Göran Hultén, Lillemor Mattsson PLoS One Research Article Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. We have previously shown that arachidonate 15-lipoxygenase B (ALOX15B) is highly expressed in atherosclerotic carotid plaques, and elucidation of mechanisms downstream of activated lipoxygenases may be relevant to our understanding of the genesis of atherosclerotic diseases. We examined 120 carotid plaques from patients with symptomatic carotid artery stenosis and showed that the extent of ALOX15B staining was significantly increased in carotid plaques with thrombosis. Impedance aggregometry analyses showed that the ALOX15B enzyme products 15-HETE and 15-HPETE increased platelet aggregation. By using a calibrated automatic thrombin assay, we showed that the ALOX15B products also increased both peak levels of thrombin and the total endogenous thrombin potential. Moreover, platelet aggregation was increased by addition of cell lysates from ischemic human macrophages, whereas platelet aggregation was reduced after knockdown of ALOX15B in human macrophages. Our data show that ALOX15B expression in human carotid plaques is associated with thrombus formation and that enzyme products of ALOX15B increase platelet aggregation and thrombin generation. We therefore propose that activated ALOX15B in macrophages may play a role in the induction of atherothrombotic events by increasing platelet aggregation and thrombin generation. Public Library of Science 2014-02-12 /pmc/articles/PMC3922896/ /pubmed/24533104 http://dx.doi.org/10.1371/journal.pone.0088546 Text en © 2014 Vijil et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vijil, Carolina Hermansson, Cecilia Jeppsson, Anders Bergström, Göran Hultén, Lillemor Mattsson Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation |
title | Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation |
title_full | Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation |
title_fullStr | Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation |
title_full_unstemmed | Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation |
title_short | Arachidonate 15-Lipoxygenase Enzyme Products Increase Platelet Aggregation and Thrombin Generation |
title_sort | arachidonate 15-lipoxygenase enzyme products increase platelet aggregation and thrombin generation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3922896/ https://www.ncbi.nlm.nih.gov/pubmed/24533104 http://dx.doi.org/10.1371/journal.pone.0088546 |
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